Time release calcium sulfate matrix for bone augmentation

ABSTRACT

An implant composition having controlled resorption rate in vivo for stimulating bone growth, a method of making the implant composition, and a kit of implant materials are disclosed. The implant composition includes a calcium sulfate compound, polymer containing particles, and a setting agent for setting the calcium sulfate compound and the polymer containing particles into a heterogeneous solid composition. Upon setting, the calcium sulfate compound forms a matrix and the polymer containing particles settled within the matrix. The resorption rate of the implant composition in vivo can be controlled of between eight and twenty-four weeks, which substantially matches the rate of bone growth. The implant composition of the present invention can be used for the repair, augmentation, and other treatment of bone.

REFERENCE TO RELATED APPLICATION

This application corresponds in part to the subject matter to that ofProvisional Application serial No. 60/223,624, filed Aug. 7, 2000, whichis herein incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

The repair of bone defects and augmentation of existing bone oftenrequire the use of permanent bio-resorbable materials. Such materialsmay include autogenous bone graft, allogeneic graft, allogeneic bonegraft, or alloplastic materials inclusive of various calcium phosphateceramics, calcium phosphate cements, calcium sulfate materials, bioglassmaterials, and composites or other combinations thereof. Calciumsulfate, which is a form of plaster of paris, is a fully bioresorbablematerial which, for sometime, has been commonly used in cement andpellet form to repair bone defects.

When calcium sulfate is used as a cement to fill a bone void, fracture,or other defect, this material dissolves at a rapid rate, i.e.,approximately one millimeter per week from the exterior of the cementtowards the center thereof. Research of the present inventors has shownthat this material causes precipitation of calcium phosphate deposits asit is resorbed at the surgical site. These precipitates, it has beenshown, stimulate and direct the formation of new bone. On the otherhand, it is important for purposes of optimal result that calciumsulfate, calcium phosphate, or any other bone repair material stay atthe surgical site for a considerable period of time in order to inhibitsoft tissue filling of the defect and to stimulate bone repair. However,currently used calcium sulfate materials are resorbed by human bonewithin two to seven weeks, depending upon the calcium sulfate form andthe particular surgical site, which cannot be retained at the site forlonger periods. As noted, such material is resorbed faster than it canbe replaced by new bone thereby reducing its value to both patient andpractitioner.

As such, the principal concern and difficulty expressed by practitioners(such as orthopedics or maxiofacial surgeons) are that calcium sulfatematerials bio-resorb or dissolve too rapidly at a surgical or arecipient site, and, thereby, outpace the formation of new bone in humanpatients. Therefore, a need arises for improved calcium sulfate basedcompositions which can resorb at the recipient site in a rate desirablymatching the rate bone growth.

SUMMARY OF THE INVENTION

The present invention relates to an implant composition havingcontrolled resorption rate in vivo for stimulating bone growth, a methodof making the implant composition, and a kit of implant materials.

In one aspect of the present invention, an implant composition havingcontrolled resorption rate comprises a calcium sulfate compound, polymercontaining particles, and a setting agent for setting the calciumsulfate compound and the polymer containing particles into aheterogeneous solid composition. Upon setting, the calcium sulfatecompound forms a matrix and the polymer containing particles settledwithin the matrix.

In another aspect, the present invention comprises a method of usingimplant materials to make the inventive implant composition for boneaugmentation and bone defect reparation. The method comprises the stepsof: (a) mixing a calcium sulfate compound and polymer containingparticles with a setting agent into a mixture, (b) applying the mixture,either by filling in a recipient site with the mixture, or by coatingthe mixture on a surface of a surgical implant prior to introducing thesurgical implant into the recipient site, and (c) setting the mixtureinto a heterogeneous solid composition.

In a further aspect, the present invention relates to a kit of implantmaterials for bone augmentation and bone defect reparation. The kitcomprises (a) dry powder of a calcium sulfate compound, and (b) polymercontaining particles. The kit can further comprise a setting agentpacked in a container, and instructions on how to use the kit forpreparing the implant composition.

It is accordingly an object of the present invention to provide animplant composition for the repair and augmentation of bone defects.

It is another object of the invention to provide an implant compositionhaving controllable resorption rate in vivo, wherein the rate ofresorption can be substantially matched to the rate of bone growth in aspecific medical or dental application.

It is a further object of the invention to provide implant materials anda method for making the implant composition.

The above and yet other objects and advantages of the present inventionwill become apparent from the hereinafter set forth Brief Description ofthe Drawings and Detailed Description of the Invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of an implant composition of one embodimentof the present invention immediately after introduction into a recipientsite, showing the heterogeneous solid implant composition.

FIG. 2 is a view, sequential to that of FIG. 1, showing a first phase ofbioresorption of the implant composition at the recipient site.

FIG. 3 is a view sequential to that of FIG. 2 showing the beginning ofresorption of the polymer containing particles of the implantcomposition.

FIG. 4 is a view, sequential to that of FIG. 3, showing the end resultof the bioresorption of the implant composition, which resultsstimulated bone growth with diminishing level of the implantcomposition.

FIG. 5 is a cross-sectional schematic view of the implant composition ofthe present invention used with a surgical implant which has buttressthreads.

FIGS. 6 and 7 show a cross-sectional schematic view and a top view,respectively, of the implant composition of the present invention usedwith a surgical implant which has a smooth exterior surface.

DETAILED DESCRIPTION OF THE INVENTION

In one aspect of the present invention, an implant composition havingcontrolled resorption rate comprises a calcium sulfate compound, polymercontaining particles, and a setting agent for setting the calciumsulfate compound and the polymer containing particles into aheterogeneous solid composition. Upon setting, the calcium sulfatecompound forms a matrix (M) and the polymer containing particles (P)settled within the matrix. FIG. 1 shows a cross-sectional schematic viewof the heterogeneous solid implant composition before resorption occurs.

In another aspect, the present invention comprises a method of usingimplant materials to make the inventive implant composition for boneaugmentation and bone defect reparation. The method comprises the stepsof: (a) mixing a calcium sulfate compound and polymer containingparticles with a setting agent into a mixture, (b) filing a recipientsite with the mixture, and (c) setting the mixture into a heterogeneoussolid composition.

The calcium sulfate compound is dry powder of calcium sulfatehemihydrate. Suitable setting agents include water, alkaline metal saltsolutions such as a saline solution, and an accelerant aqueous solutioncontaining potassium salt. The setting agents set the implant materialsinto a heterogeneous solid composition, or a multiphasic cement withdifferent speeds. The speed of setting can be controlled from sevenminutes to one hour, depending on the setting agent used as well asdesired surgical application. Among various setting agents, potassiumsalt solutions result in the fastest setting. For the purpose of thepresent invention, an aqueous solution containing potassium or sodiumions are preferably used. Most preferably, an aqueous solutioncontaining potassium ions can be used. Suitable examples of potassiumsalts include potassium sulfate, potassium phosphate, and potassiumfluoride. The concentration of potassium ion controls the speed ofsetting, the higher it is the faster the setting process. Preferably,the concentration of the potassium ions is in a range from about 0.01molar to about 0.5 molar.

The polymer containing particles (P) comprises a calcium sulfatecompound, and at least one resorbable polymer. The calcium sulfatecompound in the polymer containing particles can be calcium sulfatedihydrate, also called preset calcium sulfate, or calcium sulfatehemihydrate, also called unset calcium sulfate, or a mixture thereof. Inone embodiment, the calcium sulfate compound is mixed with a resorbablepolymer to form the particles. The amount of resorbable polymer used inthe particles controls resorption rate of the implant composition whenit is implanted in a recipient site. In an alternative embodiment, thecalcium sulfate compound of the particles is encapsulated in a coating(C) of a resorbable polymer, as shown in FIG. 1. In this case, thicknessof the resorbable polymer coating controls resorption rate of theimplant composition in a recipient site. The thickness of the resorbablepolymer coating is from about 2 μm to about 50 μm. For polymers that areonly expected to last for a short time, a thin layer can be applied. Forfast-resorbing coatings, or coatings expected to last for a long time, athick coating can be applied. Furthermore, the resorbable polymercoating is not required to be a complete encapsulation. It has beenobserved that small local incomplete coatings, or coatings with defects(accidentally or intentionally), function as initial resorption sites ofthe polymer containing particles. An analogous situation can be found intime release medicine. It is known that medical pills with smallcontrolled defects (drilled or molded) in polymer coatings are sometimesused to control drug release rates. A broad range of particle sizes canbe used in the implant composition. The particle size can be determineddepended on a particular application, and recipient site. For example,small particles are more suitable for dental fillings. On the otherhand, larger pallets are more suitable for repairing bone fracture.Preferably, the particle size is more than 20 μm in diameter since whenthe particles are smaller than 20 μm, they may cause a negative foreignbody response due to activation of macrophages.

In an additional embodiment, the particles can be made having combinedcharacteristics of the two types of particles described above. Herein,the particles can include mixed calcium sulfate compound and aresorbable polymer, which are, additionally, encapsulated with aresorbable polymer coating.

In a further embodiment, the implant composition comprises two differenttypes of polymer containing particles that have different rates ofresorption. Such particles can, for example, be particles coated withdifferent polymers, combinations of coated and mixed polymers, orparticles with coating of different thickness, a typical range being 0.5to 100 micrometers.

A wide variety of resorbable polymers can be used for the implantcomposition of the present invention. Suitable resorbable polymersinclude aliphatic polyesters of alpha-hydroxy acid derivatives, such aspolyactides, polyglycolides, polydioxanone, and poly ε-caprolactone;hydrophobic polymers, such as carnuba waxes and their derivatives; watersoluble polymers, such as poly(desaminotyrosyl-tyrosine ethyl estercarbonate), hereinafter poly (DTE carbonate) and their derivatives; andtherapeutic polymers, such as those containing salicylate. A specifictype of resorbable polymer can be selected depending on the purpose ofapplications, expected bone growth speed of a particular surgical site,and environment or condition of a recipient site. For the purpose of thepresent invention, polyactides, polyglycolides and poly (DTE carbonate)are used preferably. It is known that polyactides, including D and Lisomers, and DL copolymers of polylactic acid, have a long time historyin their use as biomedical devices. These polymers are readily availablecommercially. The polyglycolides and poly (DTE carbonate) have also beenused for bone reparation.

In general, resorbable polymers resorb slower in vivo than calciumsulfate compounds. Therefore, the amount of resorbable polymer used inthe particles, mixed or coated, controls resorption rate of the implantcomposition when it is implanted in a recipient site. The polymercontaining particles can comprise about 0.1% to about 50% (w/w) of aresorbable polymer, with about 1.5% defining the best mode. When theamount of a resorbable polymer is too high, it may cause a negativebody, that is, immune response. When used as a coating only, the above(w/w) range is about 0.1% to about 22%. The rate of resorption of theimplant composition can be controlled of between three (3) and twentyeight (28) weeks, depending on the types and amount of polymers used.

In an additional embodiment, the present invention relates to a methodof preparing the polymer containing particles. The polymer containingparticles can be prepared by two methods: (1) a surface coating process,and (2) bulk mixing of polymer and calcium sulfate. In the surfacecoating process, preformed calcium sulfate particles are mixed with apolymer solution. The polymer solution forms a liquid coating on thecalcium sulfate particles, and is allowed to dry and to form a polymersurface coating on the particles. The coating thickness and amount ofpenetration into the calcium sulfate depend on the concentration ofpolymer in the solution, and viscosity of the solution. Examples ofsuitable organic solvent can be used to dissolve the polymer and makethe polymer solution include acetone and chloroform. In the bulk mixingmethod, a fine granular form of a polymer is mixed with a granular formof calcium sulfate. The mixture is then pressed or rolled into largerparticles.

FIG. 1 to FIG. 4 illustrate the resorption process of the implantcomposition of the present invention, and the mechanism of controlledresorption rate for a proper stimulation of bone growth. FIG. 1 showsthe structure of the heterogeneous solid implant composition after themixture of calcium sulfate compound, polymer encapsulated particles, andthe setting agent is being applied in a recipient site, and set into aheterogeneous solid composition. FIG. 2 shows the first phase ofbioresorption of the implant composition. The calcium sulfate compoundin the matrix resorbs first, that is, the first two to four weeks afterimplantation, thereby forming a porous system which will fill withgranulation tissue (G) during said timeframe. The process of resorbingcalcium sulfate forms deposits of calcium phosphate (CP) which hasfunction to encourage early bone ingrowth (B).

FIG. 3 shows the second phase of the resorption, i,e., resorption of thepolymer containing particles. This occurs as early as four weeks or aslate as twenty weeks after applying the implant composition, dependingupon the particular formulation of the composition and application. Inthe example, as reflected in FIG. 3, the polymer coating has partiallybroken down allowing resorption of the encapsulated calcium sulfatecompound. Therein, the resorbing calcium sulfate compound producesdeposits of calcium phosphate (CP) as in the first phase of resorption(see FIG. 2), and additional bone ingrowth will occur.

FIG. 4 shows the end result of the resorption of the implantcomposition. This occurs as early as six weeks or as late as twenty fourweeks depending upon the particular formulation of the composition andapplication. By this time only residual amount of polymer materialremains and full bone ingrowth has occurred. In addition, most calciumphosphate deposits have been removed by bone remodeling, only a smallamount of calcium phosphate deposits within the original particles canstill be visible in new bone growth. It is understood that boneremodeling is a natural process that normally occurs very slowly.Remodeling occurs as new bone is constantly formed by osteoblasts andremoved by osteoclasts. The balance of the two processes represents anequilibrium that determines how much bone is present at any given time.However, remodeling is rapid during healing, and virtually all of theimmature bone that is formed during early healing is remodeled andreplaced by more mature bone. The calcium phosphate deposits formed bythe dissolving calcium sulfate are similar to bone mineral, and are alsoremodeled and replaced by more mature bone during this period of time.

The implant composition of the present invention can be used for therepair, augmentation, and other treatment of bone. The implantcomposition possesses significant advantages over existing calciumsulfate cements and pellets used clinically for bone repair andregeneration. More particularly, current calcium sulfate materials areresorbed by human bone within two to seven weeks, depending upon thecalcium sulfate form and the particular surgical site, however, cannotbe retained at the site for longer periods. As noted, such material isresorbed faster than it can be replaced by new bone thereby reducing itsvalue to both patient and practitioner. The implant composition of thepresent invention can be designed to resorb in phases in accordance withthe needs of a specific surgical application and environment of arecipient site, therein allowing substantial control of resorption rate.The resorption rate can be controlled of between eight and twenty fourweeks, which substantially matches the rate of bone growth.

On the other hands, since methods involving separate use of calciumsulfate and polymeric components have long been established as safe andfully bioresorbable, clinical utilities and feasibility of the presentinvention are apparent. In particular, the implant composition of thepresent invention can be applied in dentistry for bone repairing andaugmentation with or without a surgical implant.

FIG. 5 shows an example of using the implant composition of the presentinvention with a surgical implant. As shown, a surgical implant 10 isfurnished at a surgical site 12 for the purpose of establishingbio-integration with surrounding bone tissue 14. An implant of the typeof implant 10 includes buttress treads 16 (or other threading) and anintegral collar 18 which comprises an upper part 20 and a lower part 22.Located above bone tissue 14 is a cortical bone layer 24, an optionalbio-resorbable barrier layer 26 (described below) and a gum or softtissue layer 28. The implant composition 30 of the present invention isfilled in between bone tissue 14 and surgical implant 10 as anosseo-stimulative. It is to be understood that the implant compositioncan be applied to implant 10 before insertion into the osseotomy site orcan be applied to the site 12, prior to insertion of the implant.Further, any of the surfaces of implant 10 inclusive of parts 20 and 22of the collar 18 can be provided with cell growth stimulativemicrogeometry in accordance with our co-pending Application Ser. No.09/500,038. When a surgical implant exhibits an entirely smooth externalgeometry, as is the case with an implant 50 in FIG. 6, anosseo-stimulative surface 52 (FIG. 7) made of the implant composition ofthe present invention is more suitable when physically adhered to theimplant at a pre-operative site. It is, however, to be appreciated thata paste of the implant composition can be applied to an osseotomy sitein combination with use of implant 50 and its osseo-stimulative surface52.

The implant materials of the present invention can be sold as a kit. Thekit can comprise dry powder of calcium sulfate compound, one or moretypes of polymer containing particles. The kit can further comprise asetting agent packed in a container. The kit can also includeinstructions on how to prepare the implant mixture, apply it in arecipient site and set it into the solid implant composition.

While there has been shown and described the preferred embodiment of theinstant invention it is to be appreciated that the invention may beembodied otherwise than is herein specifically shown and described andthat, within said embodiment, certain changes may be made in the formand arrangement of the parts without departing from the underlying ideasor principles of this invention as set forth herewith.

We claim:
 1. An implant composition for stimulating bone growth,comprising: (a) a first calcium sulfate compound, (b) polymer containingparticles comprising a second calcium sulfate compound, and at least oneresorbable polymer, and (c) a setting agent for setting said calciumsulfate compound and said polymer containing particles into aheterogeneous solid composition, wherein upon setting, said calciumsulfate compound forms a matrix and said polymer containing particlesare settled within said matrix.
 2. The implant composition of claim 1,wherein a rate of resorption of said implant composition in a recipientsite is in a range from about four weeks to about twenty eight weeks. 3.The implant composition of claim 1, wherein said matrix and said polymercontaining particles resorb at different rates in a recipient site, andresorption of said polymer containing particles being slower.
 4. Theimplant composition of claim 1, wherein said first calcium sulfatecompound is calcium sulfate hemihydrate.
 5. The implant composition ofclaim 1, wherein said setting agent is selected from the groupconsisting of water, an alkaline metal salt solution, and a potassiumsalt solution.
 6. The implant composition of claim 1, wherein size ofsaid polymer containing particles is more than 20 μm in diameter.
 7. Theimplant composition of claim 1, wherein said second calcium sulfatecompound in said polymer containing particles is selected from the groupconsisting of calcium sulfate dihydrate, calcium sulfate hemihydrate,and mixture thereof.
 8. The implant composition of claim 1, wherein saidresorbable polymer is mixed with said calcium sulfate compound of saidparticles.
 9. The implant composition of claim 1, wherein said calciumsulfate compound of said particles is coated with a resorbable polymercoating.
 10. The implant composition of claim 9, wherein thickness ofsaid resorbable polymer coating is from about 2 μm to about 50 μm. 11.The implant composition of claim 1, wherein said resorbable polymer isaliphatic polyesters of alpha-hydroxy acid derivatives.
 12. The implantcomposition of claim 11, wherein said resorbable polymer is selectedfrom the group consisting of polyactides, polyglycolides, polydioxanone,and poly ε-caprolactone.
 13. The implant composition of claim 11,wherein said resorbable polymer is polyactides.
 14. The implantcomposition of claim 1, wherein said resorbable polymer is apoly(desaminotyrosyl-tyrosine ethyl ester carbonate).
 15. The implantcomposition of claim 1, wherein said resorbable polymer is selected fromthe group consisting of hydrophobic polymers, carnuba waxes, watersoluble polymers, polyvinyl alcohols, and therapeutic polymerscontaining salicylates.
 16. The implant composition of claim 1, whereinthe amount of said resorbable polymer in said polymer containingparticle is in a range from about 0.1% to about 50% (w/w).
 17. A kit ofimplant materials for bone augmentation and bone defect reparationcomprising: (a) dry powder of a first calcium sulfate compound, and (b)polymer containing particles comprising a second calcium sulfatecompound, and at least one resorbable polymer.
 18. The kit of implantmaterials of claim 17, wherein said first calcium sulfate compound iscalcium sulfate hemihydrate.
 19. The kit of implant materials of claim17, wherein size of said polymer containing particles is more than 20 μmin diameter.
 20. The kit of implant materials of claim 17, wherein saidsecond calcium sulfate compound in said polymer containing particles isselected from the group consisting of calcium sulfate dihydrate, calciumsulfate hemihydrate, and mixture thereof.
 21. The kit of implantmaterials of claim 17, wherein said resorbable polymer is mixed withsaid calcium sulfate compound of said particles.
 22. The kit of implantmaterials of claim 17, wherein said calcium sulfate compound of saidparticles is coated with a resorbable polymer coating.
 23. The kit ofimplant materials of claim 22, wherein thickness of said resorbablepolymer coating is from about 2 μm to about 50 μm.
 24. The kit ofimplant materials of claim 17, wherein said resorbable polymer isaliphatic polyesters of alpha-hydroxy acid derivatives.
 25. The kit ofimplant materials of claim 24, wherein said resorbable polymer isselected from the group consisting of polyactides, polyglycolides,polydioxanone, and poly ε-caprolactone.
 26. The kit of implant materialsof claim 24, wherein said resorbable polymer is polyactides.
 27. The kitof implant materials of claim 17, wherein said resorbable polymer is apoly(desaminotyrosyl-tyrosine ethyl ester carbonate).
 28. The kit ofimplant materials of claim 17, wherein said resorbable polymer isselected from the group consisting of hydrophobic polymers, carnubawaxes, water soluble polymers, polyvinyl alcohols, and therapeuticpolymers containing salicylates.
 29. The kit of implant materials ofclaim 17, wherein the amount of said resorbable polymer in said polymercontaining particle is in a range from about 0.1% to about 30% (w/w).30. The kit of implant materials of claim 17, wherein said kit comprisestwo different polymer containing particles that resorb at differentrates in a recipient site.
 31. The kit of implant materials of claim 17further comprising a setting agent, packed in a container.
 32. The kitof implant materials of claim 31, wherein said setting agent is selectedfrom the group consisting of water, an alkaline metal salt solution, anda potassium salt solution.
 33. The kit of implant materials of claim 17further comprising instructions on how to use the kit.
 34. A method forbone augmentation and bone defect reparation comprising the steps of:(a) mixing a calcium sulfate compound and resorbable polymer coatedparticles with a setting agent into a mixture, (b) applying saidmixture, and (c) setting said mixture into a heterogeneous solidcomposition, wherein upon setting, said calcium sulfate compound forms amatrix and said resorbable polymer coated particles settled within saidmatrix; wherein said heterogeneous solid composition resorbs at acontrolled rate in a recipient site for stimulating bone growth.
 35. Themethod of claim 34, wherein applying said mixture is filling a recipientsite with said mixture.
 36. The method of claim 34, wherein applyingsaid mixture is coating said mixture on a surface of a surgical implantprior to introducing said surgical implant into said recipient site. 37.The method of claim 34, wherein said setting agent controls a speed ofsetting said mixture into a heterogeneous solid composition.
 38. Themethod of claim 37, wherein said setting agent is selected from thegroup consisting of water, an alkaline metal salt solution, and apotassium salt solution.
 39. The method of claim 34, wherein saidresorbable polymer coated particles resorbable polymer coated particlesthat resorb at different rates in a recipient site.
 40. An implantcomposition for stimulating bone growth, comprising: (a) a calciumsulfate compound, (b) resorbable polymer coated particles, and (c) asetting agent for setting said calcium sulfate compound and saidresorbable polymer coated particles into a heterogeneous solidcomposition, wherein upon setting, said calcium sulfate compound forms amatrix and said resorbable polymer coated particles are settled withinsaid matrix.
 41. The implant composition of claim 40, wherein saidmatrix and said resorbable polymer coated particles resorb at differentrates in a recipient site, and resorption of said resorbable polymercoated particles being slower.
 42. The implant composition of claim 41,wherein a rate of resorption of said implant composition in a recipientsite is in a range from about four weeks to about twenty eight weeks.43. The implant composition of claim 41, wherein said calcium sulfatecompound is calcium sulfate hemihydrate.
 44. The implant composition ofclaim 41, wherein said setting agent is selected from the groupconsisting of water, an alkaline metal salt solution, and a potassiumsalt solution.
 45. The implant composition of claim 41, wherein saidresorbable polymer coated particles comprise: (a) a calcium sulfatecompound, and (b) a polymer coating with at least one resorbablepolymer.
 46. The implant composition of claim 45, wherein size of saidresorbable polymer coated particles is more than 20 μm in diameter. 47.The implant composition of claim 45, wherein said calcium sulfatecompound in said resorbable polymer coated particles is selected fromthe group consisting of calcium sulfate dihydrate, calcium sulfatehemihydrate, and mixture thereof.
 48. The implant composition of claim47, wherein thickness of said polymer coating is from about 2 μm toabout 50 μm.
 49. The implant composition of claim 48, wherein saidresorbable polymer is aliphatic polyesters of alpha-hydroxy acidderivatives.
 50. The implant composition of claim 49, wherein saidresorbable polymer is selected from the group consisting of polyactides,polyglycolides, polydioxanone, and poly ε-caprolactone.
 51. The implantcomposition of claim 49, wherein said resorbable polymer is polyactides.52. The implant composition of claim 48, wherein said resorbable polymeris a poly(desaminotyrosyl-tyrosine ethyl ester carbonate).
 53. Theimplant composition of claim 48, wherein said resorbable polymer isselected from the group consisting of hydrophobic polymers, carnubawaxes, water soluble polymers, polyvinyl alcohols, and therapeuticpolymers containing salicylates.
 54. The implant composition of claim48, wherein the amount of said resorbable polymer in said resorbablepolymer coated particles is in a range from about 0.1% to about 50%(w/w).
 55. A kit of implant materials for bone augmentation and bonedefect reparation comprising: (a) dry powder of a calcium sulfatecompound, and (b) resorbable polymer coated particles.
 56. The kit ofimplant materials of claim 55, wherein said calcium sulfate compound iscalcium sulfate hemihydrate.
 57. The kit of implant materials of claim55, wherein said resorbable polymer coated particles comprise: (a) acalcium sulfate compound, and (b) a polymer coating with at least oneresorbable polymer.
 58. The kit of implant materials of claim 57,wherein size of said resorbable polymer coated particles is more than 20μm in diameter.
 59. The kit of implant materials of claim 57, whereinsaid calcium sulfate compound in said resorbable polymer coatedparticles is selected from the group consisting of calcium sulfatedihydrate, calcium sulfate hemihydrate, and mixture thereof.
 60. The kitof implant materials of claim 59, wherein thickness of said polymercoating is from about 2 μm to about 50 μm.
 61. The kit of implantmaterials of claim 60, wherein said resorbable polymer is aliphaticpolyesters of alpha-hydroxy acid derivatives.
 62. The kit of implantmaterials of claim 61, wherein said resorbable polymer is one selectedfrom the group consisting of polyactides, polyglycolides, polydioxanone,and poly ε-caprolactone.
 63. The kit of implant materials of claim 61,wherein said resorbable polymer is polyactides.
 64. The kit of implantmaterials of claim 60, wherein said resorbable polymer is apoly(desaminotyrosyl-tyrosine ethyl ester carbonate).
 65. The kit ofimplant materials of claim 60, wherein said resorbable polymer isselected from the group consisting of hydrophobic polymers, carnubawaxes, water soluble polymers, polyvinyl alcohols, and therapeuticpolymers containing salicylates.
 66. The kit of implant materials ofclaim 60, wherein the amount of said resorbable polymer in saidresorbable polymer coated particles is in a range from about 0.1% toabout 30% (w/w).
 67. The kit of implant materials of claim 57, whereinsaid kit comprises two different resorbable polymer coated particlesthat resorb at different rates in a recipient site.
 68. The kit ofimplant materials of claim 57, further comprising a setting agent,packed in a container.
 69. The kit of implant materials of claim 68,wherein said setting agent is selected from the group consisting ofwater, an alkaline metal salt solution, and a potassium salt solution.